Digital Commons Network^™

Precision Drug Delivery For Vancomycin Efficacy And Safety In Critically Ill Patients, Alexander Flannery

Theses and Dissertations--Clinical and Translational Science

Vancomycin is the most commonly prescribed antibiotic for hospitalized patients. Despite this fact and decades of clinical use, clinicians remain challenged to meet dosing targets of this narrow therapeutic index drug as well as minimize the risks of therapy, primarily nephrotoxicity. These concerns are magnified in critically ill patients given their severity. Accordingly, in a series of five clinical studies, we sought to identify optimal methods of vancomycin administration in critically ill patients to maximize efficacy and minimize nephrotoxicity via three techniques: use of continuous versus intermittent infusion, use of first-dose pharmacokinetic calculations to guide dosing, and use of loading …

Therapeutic Drug Monitoring Of Beta-Lactam Antibiotics In Critically Ill Patients With Sepsis, Melissa Thompson Bastin

Theses and Dissertations--Clinical and Translational Science

Sepsis is a devastating diagnosis affecting over 750,000 patients a year, accounting for approximately 10% of all hospital admissions, costs more than $50,000 per patient, and exceeds $17 billion annual spending. The mortality rate for sepsis remains unacceptably high: one out of every three patients diagnosed with sepsis dies. Sepsis physiology induces physiologic changes to drug pharmacokinetic (PK) parameters that alter the ability to achieve the goal pharmacodynamic (PD) target for beta-lactams of >4-fold unbound concentration above the minimum inhibitory concentration for 100% of the dosing interval (100% fT >4x MIC). Sepsis treatment such as volume resuscitation and vasopressor …

The Roles Of The Actin Network And Co-Opted Host Factors In Tbsv Replication, Melissa Gabriela Molho Medina

Theses and Dissertations--Plant Pathology

Positive-stranded (+) RNA viruses are the largest family of viruses that infect plants, causing important economic losses in different crops. Tomato bushy stunt virus (TBSV), a small positive-stranded RNA virus, has emerged as a model virus to study virus-host interactions. TBSV encodes for only five proteins, therefore, to infect the host cell TBSV co-opts selected host components and subverts specific molecular pathways.

Firstly, I performed a proteomic screening using Arabidopsis proteins. I found that TBSV viral replication proteins interact with 88 host proteins, including the ubiquitin-conjugating enzyme 2 (Ubc2), fructose 1,6 biphosphate aldolase (Fba1), and several members of the Hps70 …

Muscle Mass And Immune Function In The Senior Horse, Alisa Christina Herbst

Theses and Dissertations--Veterinary Science

Senior horses (≥ 15 years) represent up to one-third of the global equine population, and the proportion of old horses (≥ 20 years) in the U.S. has been steadily increasing. Aging is associated with a loss of skeletal muscle mass in horses, and while age-related muscle loss is comparingly well characterized in humans, little is currently known concerning underlying mechanisms, adverse outcomes, or the prevalence of low muscle mass in senior horses. One factor proposed to play a role in the development of age-related muscle atrophy in humans is inflamm-aging, a low-grade inflammation that affects elderly people and that has …

Equine West Nile Virus In Kentucky: Characteristics Of Historical Testing And Analysis Of Causal Factors, Kaelyn Short

Theses and Dissertations--Public Health (M.P.H. & Dr.P.H.)

As the arbovirus with the highest incidence in both humans and horses in the United States, West Nile Virus (WNV) presents a significant risk to the equine population of Kentucky. Widespread infection has the potential to cause a significant economic impact to the state and long-term health complications for the horses. To better understand the burden of equine WNV, historical diagnostic testing archives the University of Kentucky Veterinary Diagnostic Lab were analyzed along with environmental and census data collected from additional sources. A total of 2146 test results were analyzed utilizing descriptive statistics, chi-square tests of independence, and binary logistic …

Toward Improving Physician/Patient Communication Regarding Invisible Chronic Illness (Ici): The Potential Of Mhealth Technology In Instructional Communication, Jami Leigh Warren, Karen Clancy, Christy F. Brady, Kendall Rump, Tayla New-Oglesby

Health and Clinical Sciences Faculty Publications

Patients that suffer from invisible chronic illness (ICI) such as autoimmune conditions, neurological conditions, and gastrointestinal problems often struggle to obtain a proper medical diagnosis due to a lack of objective indicators to help health-care providers diagnose patients with ICIs. Thus, researchers conducted interviews with 21 participants with Postural Orthostatic Tachycardia Syndrome (POTS) to determine what messages they received from health-care providers as they pursued a diagnosis, how they interpreted those messages, and what role mHealth technology may play in improving patient/provider communication and effective diagnosis/treatment of ICIs. Several themes regarding potential instructional communication intervention content emerged from the interview …

Myelin, Cpla2, And Azithromycin: Modulation Of Macrophage Activation In Spinal Cord Injury Inflammation, Timothy J. Kopper

Theses and Dissertations--Physiology

Spinal cord injury (SCI) produces a chronic inflammatory state primarily mediated by macrophages consisting of resident microglia and infiltrating monocytes. These chronically activated SCI macrophages adopt a pro-inflammatory, pathological state that continues to cause additional damage after the initial injury and inhibits recovery. While the roles of macrophages in SCI pathophysiology are well documented, the factors contributing to this maladaptive response are poorly understood. Here, we identify the detrimental effects of myelin debris on macrophage physiology and demonstrate a novel, activation state-dependent role for cytosolic phospholipase-A2 (cPLA₂) in myelin- mediated potentiation of pro-inflammatory macrophage activation. Macrophage- mediated inflammatory …

Pharmacy Student Opinions Related To Question, Persuade, And Refer (Qpr) Suicide Prevention Training, Alexandra Sutphin

MPA/MPP/MPFM Capstone Projects

Suicide is one of the leading causes of death in the United States (Centers for Disease Control and Prevention [CDC], 2017). The Coronavirus Disease 2019 (COVID-19) pandemic has increased concerns related to suicide, with additional attention placed on the potential long-term negative impact of COVID-19 on mental health. Pharmacists are healthcare providers who are readily accessible and underutilized in suicide prevention efforts. This study uses survey methodology and comparative analyses to develop recommendations for the timing and administration of Question, Persuade, and Refer (QPR) suicide prevention training in the Doctor of Pharmacy (PharmD) curriculum at the University of Kentucky College …

A Biochemical Characterization Of The Fusion Proteins From Enveloped Rna Viruses, Chelsea T. Barrett

Theses and Dissertations--Molecular and Cellular Biochemistry

Enveloped viruses must bind target cells and then fuse the viral membrane with a cell membrane to enter a host cell. These viruses use one or more surface glycoproteins to carry out these critical functions. The surface glycoprotein that carries out the fusion function, termed a fusion protein, is divided into three classes based on structural similarities. Some of the most studied human viral pathogens, such as human immunodeficiency virus (HIV), Ebola virus, influenza, measles, and the recently emerged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), possess class I fusion proteins. Following synthesis, class I fusion proteins associate as non-covalently …

Substrate Trafficking Within The Type Vii Secretion Systems Of Pathogenic Mycobacteria, Zachary A. Williamson

Theses and Dissertations--Molecular and Cellular Biochemistry

Tuberculosis (TB), primarily caused by infection of Mycobacterium tuberculosis (Mtb) in the lungs, is the deadliest infectious bacterial disease killing 1.5 million people annually. A major determinant of virulence is active secretion through three specialized type VII secretion (ESX) systems; ESX-1, ESX-3, and ESX-5. A large group of substrates exported by the ESX systems is the PE (Proline-Glutamine) and PPE (Proline-Proline-Glutamate) families of proteins, which are highly expanded in the pathogenic species of Mycobacteria and encompass over 7% of Mtb’s genome coding capacity. PE and PPE proteins interact together to form PE-PPE heterodimers, and are secreted through …

Improving Multidisciplinary Adherence To A Daily Goals Checklist In The Icu: A Quality Improvement Initiative, Chelsea Mccarty

DNP Projects

Abstract

Background: In November 2019, the University of Louisville Hospital merged and assumed operations of all KentuckyOne facilities. During the transition, a spike in hospital acquired infection rates ensued at Jewish Hospital, notably amongst the critical care units. In January 2020, a daily checklist was introduced to the critical care department. A Daily Checklist is a tailored communication tool designed to reduce communication error and improve adherence to patient safety measures. There continues to be a gap in adherence to the U of L daily checklist from both nurses and providers. Purpose: The purpose of this project was to improve …

Rational Design Of Small Molecule Disruptors Of Protein-Protein Interactions: Pd-1/Pd-L1; C-Myc, Arid4b, Samuel Ofori

Theses and Dissertations--Chemistry

Protein-protein interactions (PPIs) are vital to many biological processes, including gene expression, and immune reactions to pathogens. There are approximately 650,000 PPIs in humans with pertinent physiological functions. Aberrant expression of PPIs lead to improper function and contribute to a plethora of disease conditions including cancer. Thus, PPIs represent an enormous target space for drug discovery and chemical probes. Direct targeting of clinically relevant PPIs with small molecules remains an unmet medical need. Development of small-molecule inhibitors of PPIs is a challenging enterprise and in most cases considered undruggable due to large protein surfaces, lack of deep binding pockets and …

Investigation Of Multidrug Efflux Transporter Acrb In Escherichia Coli: Assembly, Degradation And Dynamics, Prasangi Irosha Rajapaksha

Theses and Dissertations--Chemistry

The Resistant Nodulation Division (RND) super family member, tripartite AcrA-AcrB-TolC efflux pump, is a major contributor in conferring multidrug-resistance in Escherichia coli. The structure of the pump complex, and drug translocation by functional rotation mechanism have been widely studied. Despite of all these data, the dynamics of the assembly process of the pump and AcrB during functional rotation in the process of drug efflux remains poorly understood. My thesis focuses on understanding the pump assembly process, dynamics of AcrB in functional rotation mechanism, and also investigate the mechanism of degradation of AcrB facilitated by a C-terminal ssrA tag.

In the …

Probing The Assembly, Functional Relevance, And Dynamics Of Acra In Multi Drug Efflux In Escherichia Coli, Isoiza Ojo

Theses and Dissertations--Chemistry

Efflux pumps and low permeability of the outer membrane of gram-negative bacteria are major culprits in drug resistance. The most studied of these multidrug efflux pumps is the AcrAB-TolC, a complex of three proteins, the inner membrane transporter AcrB, the periplasmic adaptor AcrA and outer membrane factor TolC. This pump exports a wide range of molecules such as dyes, detergents, and antibiotics out of the bacteria system into the external environment. AcrB and TolC exist as obligate trimers, but the structure of AcrA during the assembly process is not well defined. My research aims to explore the functional and structural …

Development Of Novel Polymeric Materials For Their Application In Monitoring And Remediation Of Environmental Pollutants, Rishabh Shah

Theses and Dissertations--Chemical and Materials Engineering

Remediation of environmental pollutants from water is one of the major challenges in the 21st century. Utilizing novel polymeric materials to accomplish this challenge has garnered a lot of interest in recent times. Flexibility in synthesizing as well as functionalizing makes them attractive for their application in pollutant remediation. This work is based on development and characterization of novel crosslinked polymeric as well as linear polymeric materials from biphenyl-based monomers, biphenyl based crosslinker and a temperature responsive monomer (Nisopropylacrylamide (NIPAAm)) for their application in remediation of toxic pollutants such as polychlorinated biphenyls (PCBs), polyaromatic hydrocarbons (PAHs) and iron oxide nanoparticle …

Impact Of Ptsd On Hcv/Hiv Risk-Reduction Interventions Among Incarcerated Drug-Using Women In Rural Appalachia, Caitlyn Hood

Theses and Dissertations--Psychology

Justice-involved women in rural Appalachian Kentucky are a particularly vulnerable group in need of targeted risk-reduction interventions for hepatitis C virus (HCV) and human immunodeficiency virus (HIV). Compared to women in the general U.S. population, justice-involved women in rural Appalachia report dramatically higher rates of HCV/HIV risk behaviors (e.g., injection drug use and risky sex), interpersonal violence (IV; e.g., physical, sexual, or emotional abuse), and posttraumatic stress disorder (PTSD). IV and PTSD may exacerbate rural Appalachian women’s risk for contracting and transmitting HIV/HCV, indicating a need to approach HCV/HIV risk-reduction interventions from a trauma-informed perspective.

Brief motivational interviewing and psychoeducation …

Investigating How Timing Of Case Study Presentation On Huntington Disease Influences Construction Of Argument Warrant While Learning The Central Dogma Of Molecular Biology, Katherine A. Sharp

Theses and Dissertations--Education Sciences

A common belief among pre-medical and medical students is that biochemistry is not relevant to practicing medicine. Among topics commonly taught in biochemistry, courses include the Central Dogma of Molecular Biology, which is among the most critical science topics taught to medical students by biochemistry educators. Perceived irrelevance among students may be due to common curricular trends in biochemistry education. Many biochemistry courses are found at Research I (R1) universities that teach biochemistry using traditional lectures with little evidence of supporting learning with real-world applications. Instructors commonly assume that students can make realworld connections independently during lecture courses, but it …

An Overview Of The Effect Of Bioaerosol Size In Coronavirus Disease 2019 Transmission, Marcelo I. Guzman

Chemistry Faculty Publications

The fast spread of coronavirus disease 2019 (COVID-19) constitutes a worldwide challenge to the public health, educational and trade systems, affecting the overall well-being of human societies. The high transmission and mortality rates of this virus, and the unavailability of a vaccine or treatment, resulted in the decision of multiple governments to enact measures of social distancing. Such measures can reduce the exposure to bioaerosols, which can result in pathogen deposition in the respiratory tract of the host causing disease and an immunological response. Thus, it is important to consider the validity of the proposal for keeping a distance of …

Syphilis Hepatitis Presenting As A Mimic Of Primary Biliary Cholangitis, Cody Kern, Ahmed Elmoursi, Caroline Blake, Andrew Hoellein

Internal Medicine Faculty Publications

Syphilis hepatitis is a rare cause of acute liver injury. Primary biliary cholangitis (PBC) is a progressive autoimmune disease characterized by the typical presentation of a cholestatic liver injury and the presence of antimitochondrial antibodies (AMAs). We present a case of syphilis hepatitis that presented as a mimic to PBC with positive AMA. The eradication of syphilis led to the resolution of the liver injury and down trending of the antibody level. We recommend excluding syphilis in patients with high-risk behaviors presenting with a cholestatic liver injury and positive AMA before the diagnosis of PBC.

Behavioral And Enhanced Perinatal Intervention (B-Epic): A Randomized Trial Targeting Tobacco Use Among Opioid Dependent Pregnant Women, Amanda Fallin-Bennett, Michelle R. Lofwall, Teresa M. Waters, Paul Nuzzo, Janine Barnett, Letitia Ducas, Andrea Mccubbin, Niraj R. Chavan, Lisa Blair, Kristin Ashford

Nursing Faculty Publications

Background

Opioid use during pregnancy is a significant public health issue. The standard of care for treating opioid use disorder during pregnancy includes medications for opioid disorder (MOUD). However, tobacco use often goes unaddressed among pregnant women on MOUD. In 2018, our team received a National Institute on Drug Abuse (NIDA) funded R34 to conduct a three year-randomized trial to test the feasibility of a novel tobacco intervention for pregnant women receiving MOUD.

Aims

The aims of this study are: (1) to determine the impact of the B-EPIC intervention on maternal tobacco use and stage of change; (2) to determine …

Rural Appalachia Battling The Intersection Of Two Crises: Covid-19 And Substance Use Disorders, Margaret Miller, Rebekah Rollston, Kate E. Beatty, Michael Meit

Journal of Appalachian Health

During the COVID-19 pandemic, rural Appalachia is at great risk of unforeseen side effects including increased mortality from substance use disorders (SUDs). People living with SUDs are at increased risk for both exposure to and poor outcomes from COVID infection. The economic impacts of COVID-19 must also be considered. As rural Appalachia combats the substance use crisis amidst the COVID-19 pandemic, the geographic economic, health and social inequities within our region must be considered. As a national recovery is sought, we should reimagine federal policies that center the economic and public health of rural Appalachia addressing the two crises.

In Their Own Words: How Opioids Have Impacted The Lives Of “Everyday” People Living In Appalachia, Patricia Nola Eugene Roberson, Gina Cortez, Laura H. Trull, Katherine Allison Lenger

Journal of Appalachian Health

Introduction: The opioid epidemic is ravaging people, families, and communities in Appalachia. However, limited research has examined how “everyday” people (e.g., not chronic pain patients, not medical professionals) living in these communities how opioids have impacted their lives.

Objective: Identify the perception of the opioid epidemic on individuals, families, and communities from people living in region most impacted regions.

Methods: Patients were recruited at Remote Area Medical clinics throughout Central and Southern Appalachia to complete interviews online (N = 169) or over the phone (N = 26), including one open-ended question about how opioids have impacted their lives.

Results: Using …

Did Covid-19 Change Life Insurance Offerings?, Timothy F. Harris, Aaron Yelowitz, Charles J. Courtemanche

Institute for the Study of Free Enterprise Working Papers

The profitability of life insurance offerings is contingent on accurate projections and pricing of mortality risk. The COVID-19 pandemic created significant uncertainty, with dire mortality predictions from early forecasts resulting in widespread government intervention and greater individual precaution that reduced the projected death toll. We analyze how life insurance companies changed pricing and offerings in response to COVID-19 using monthly data on term life insurance policies from Compulife. We estimate event-study models that exploit well-established variation in the COVID-19 mortality rate based on age and underlying health status. Despite the increase in mortality risk and significant uncertainty, we find limited …

Risk Factors For Delayed Viral Suppression On First-Line Antiretroviral Therapy Among Persons Living With Hiv In Haiti, 2013-2017, Shannan N. Rich, Robert L. Cook, Lusine Yaghjyan, Kesner Francois, Nancy Puttkammer, Ermane Robin, Jungjun Bae, Nadjy Joseph, Luisa Pessoa-Brandão, Chris Delcher

Institute for Pharmaceutical Outcomes and Policy Faculty Publications

Studies of viral suppression on first-line antiretroviral therapy (ART) in persons living with human immunodeficiency virus (PLHIV) in Haiti are limited, particularly among PLHIV outside of the Ouest department, where the capital Port-au-Prince is located. This study described the prevalence and risk factors for delayed viral suppression among PLHIV in all geographic departments of Haiti between 2013 and 2017. Individuals who received viral load testing 3 to 12 months after ART initiation were included. Data on demographics and clinical care were obtained from the Haitian Active Longitudinal Tracking of HIV database. Multivariable logistic regression was performed to predict delayed viral …

Salmonella Meningitis Complicated By Ventriculitis And Brain Abscesses In An Hiv Positive Adult Patient, Tamoor Ahmed, Taha Ahmed

Internal Medicine Faculty Publications

Salmonella meningitis is a rare complication of Salmonella sepsis and is mostly reported in infants and young children. The incidence of Salmonella bacteremia is increased in immunocompromised adult individuals, such as those having human immunodeficiency virus (HIV) infection. Ventriculitis and brain abscess as a complication of Salmonella intracranial infection is particularly rare, even in patients who are immunosuppressed. Herein, we report a case of Salmonella meningitis complicated by ventriculitis and two brain abscesses in an HIV positive adult patient requiring mini-craniectomy and drainage along with a prolonged course of antibiotic therapy with a favorable outcome.

Comparative Analysis Of Intestinal Helminth Infections In Colic And Non-Colic Control Equine Patients, Heidrun Gehlen, Nadine Wulke, Antonia Ertelt, Martin K. Nielsen, Simone Morelli, Donato Traversa, Roswitha Merle, Douglas Wilson, Georg Von Samson-Himmelstjerna

Maxwell H. Gluck Equine Research Center Faculty Publications

All around the world, intestinal helminths constitute one of the most prevalent life-long occurring infections and re-infections affecting all horse age groups. A range of parasite species among strongyles, ascarids, and tapeworms is known to have the potential to cause colic in horses. However, there is a lack of current scientific evidence on the actual relevance of helminth infection levels in the context of colic in horses kept during prevailing epidemiological conditions. Thus, a prospective case-control study on the occurrence of intestinal helminths in a total of 620 mainly adult equine clinic patients was conducted to investigate the association between …

Role Reversal Of Functional Identity In Host Factors: Dissecting Features Affecting Pro-Viral Versus Antiviral Functions Of Cellular Dead-Box Helicases In Tombusvirus Replication, Cheng-Yu Wu, Peter D. Nagy

Plant Pathology Faculty Publications

Positive-stranded (+)RNA viruses greatly exploit host cells to support viral replication. However, unlike many other pathogens, (+)RNA viruses code for only a limited number of genes, making them highly dependent on numerous co-opted host factors for supporting viral replication and other viral processes during their infections. This excessive dependence on subverted host factors, however, renders (+)RNA viruses vulnerable to host restriction factors that could block virus replication. Interestingly, cellular ATP-dependent DEAD-box RNA helicases could promote or inhibit the replication of Tomato bushy stunt virus (TBSV) replication. However, it is currently unknown what features make a particular DEAD-box helicase either pro-viral …

Development And Implementation Of An Influenza Point-Of-Care Testing Service In A Chain Community Pharmacy Setting, Rachel Hardin, Pheli Roberts, Brooke Hudspeth, Angela Tracy, Lauren Baldwin, Michael Raque, Clark D. Kebodeaux

Pharmacy Practice and Science Faculty Publications

Point-of-care testing is becoming increasingly commonplace in community pharmacy settings. These tests are often used in the management of chronic disease, such as blood sugar, hemoglobin A1c and lipid levels, but can also be used for acute conditions such as influenza infection and group A streptococcus pharyngitis. When used for these acute infections, point-of-care tests can allow for pharmacist-initiated treatment. In this study, an influenza point-of-care testing service was developed and implemented in a chain community pharmacy setting and a retrospective review was conducted to assess the service. Of patients tested, 29% tested positive for influenza A and/or B; 92% …

Measuring The Spread Of Covid-19 In Kentucky: Do We Have The Right Data?, Kenneth R. Troske, Paul A. Coomes

Institute for the Study of Free Enterprise Working Papers

We examine various measures of COVID-19 infections, hospitalizations and deaths, with an emphasis on data for Kentucky. We find that: Data on the number of new reported cases of the disease obtained from convenience samples (as opposed to representative random samples) is an inaccurate measure of the spread of the disease in the State. Using CDC data and national studies, it appears that there were ten times the number of infections in March than reported for Kentucky at the time and by September the State is still capturing only one out of two people infected.

A better measure of new …

Importation Of Macrocyclic Lactone Resistant Cyathostomins On A Us Thoroughbred Farm, Martin K. Nielsen, M. Banahan, R. M. Kaplan

Maxwell H. Gluck Equine Research Center Faculty Publications

Anthelmintic resistance in equine cyathostomins is both widespread and highly prevalent in the benzimidazole and tetrahydropyrimidine classes; however, reports of resistance to macrocyclic lactone (ML) drugs are sparse and sporadic. This study reports a case of clear ML resistance in a group of Thoroughbred yearlings imported from Ireland to the US in 2019. Fecal egg count reduction (FECR) following ivermectin administered in February 2020 demonstrated 100% reduction in the US bred yearlings, but 93.5%, 70.5%, and 74.5% reduction in three groups of the imported yearlings. The two former groups were then retreated with ivermectin, yielding FECRs of 33.8% and 23.5%, …